In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by ciprofloxacin therapy

We report the emergence after 4 days of ciprofloxacin monotherapy of a doub le mutant of Pseudomonas aeruginosa overexpressing the multidrug efflux sys tem MexAB-OprM and harbouring a mutation in the gyrB gene. Compared with it s initial susceptible counterpart, this mutant exhibited a significant incr ease in resistance to most of the beta -lactam antibiotics tested (16 x MIC of ticarcillin) and to ciprofloxacin (128 x MIC). Combined ceftazidime and amikacin therapy finally eradicated the resistant isolate and cured the pa tient of his infection. This case illustrates how strains of A aeruginosa m ay develop high levels of fluoroquinolone resistance by combining efflux me chanisms and target alterations.